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Malignancies associated with tumour necrosis factor inhibitors in registries and prospective observational studies: a systematic review and meta-analysis


Objectives This project was undertaken to assess the risk of malignancy in patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors (TNFi) in clinical practice, as recorded in prospective, observational studies.

Methods The authors undertook comprehensive searches of MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and American College of Rheumatology, European League against Rheumatism and British Society for Rheumatology conference abstracts according to a prespecified protocol.

Results The searches identified 2039 full-text papers and 1979 conference abstracts, of which 21 full texts and eight abstracts met the inclusion criteria. The pooled estimate for the risk of all-site malignancy from seven studies was 0.95 (95% CI 0.85 to 1.05). Two studies reported there was no evidence that longer exposure to TNFi agents increased the risk of malignancy. In patients with previous malignancies there was a higher risk of a new/recurring malignancy. This risk was not increased further by exposure to TNFi, although CI were wide. Results from four studies showed that patients treated with TNFi have a significantly increased risk of developing a non-melanoma skin cancer (1.45, 95% CI 1.15 to 1.76). In addition, patients are at an increased risk of developing melanoma, as the pooled estimate from two studies was 1.79 (95% CI 0.92 to 2.67). The pooled estimate for the risk of lymphoma was 1.11 (95% CI 0.70 to 1.51).

Conclusions This systematic review and meta-analysis shows that TNFi treatments do not increase the risk of malignancy, particularly lymphoma. However, they do appear to increase the risk of skin cancer, including melanoma.

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  • Funding The literature searches and data extraction were funded by a grant from Wyeth Europa (Wyeth was acquired by Pfizer in October 2009) to the Evidence Research Unit. Wyeth Europa paid author travel and accommodation costs to attend meetings at which this systematic review was discussed. None of the authors received payment for their contributions to this manuscript.

  • Competing interests XM has received honoraria for talks or participation in advisory boards from Roche, UCB, Wyeth (acquired by Pfizer in October 2009). MM-C has received fees for lectures from Wyeth, Pfizer, Actelion, BMS, Roche and research grants from Pfizer, Actelion, Schering-Plough, Centocor. KP has received fees as a consultant to Abbott, Schering-Plough, Roche and Wyeth. PT has received research grants from Merck, UCB, AstraZeneca, GlaxoSmithKline and Roche. He has been an invited speaker and advisor for Abbott, Bristol-Myers Squibb, Centocor, Roche, Schering-Plough, Wyeth and UCB. RvV has received research support and honoraria from Abbott, Bristol. Myers Squibb, Roche, Schering-Plough, UCB Pharma and Wyeth. RH was supported by a grant from Wyeth Europa. CW was supported by a grant from Wyeth Europa. RL was supported by a grant from Wyeth Europa. AR was an employee of Wyeth Europa and had held shares in Wyeth and currently has Pfizer share options. Work undertaken since leaving the company in June 2010 has been funded by Pfizer. PE has received research grants and honoraria from Abbott, Bristol. Myers Squibb, Roche, MSD, UCB Pharma and Wyeth.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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